Age-Related Macular Degeneration (AMD) is a highly pervasive degenerative condition of the retina. AMD currently affects approximately one million Canadians; and the likelihood of developing AMD for people over the age of 75 years of age is 1 in 4 [1]. The initial symptoms present themselves as blurred or distorted vision and as the disease progresses the vision worsens as the central area of vision degenerates to the point of total blindness. There are two distinct stages to the progression of the condition [2]. The first stage of AMD, known as dry AMD, is characterized by the formation of lipoprotein deposits called drusen. The drusen develop on the outer layer of the retina between the Retinal Pigment Epithelium (RPE), the last layer of the retina, and the Bruch's membrane, the first layer of the choroid. These drusen cause cellular stress on the RPE cells leading to increased photoreceptor death. Eventually, dry AMD progresses to the final stage of the condition known as wet AMD where blood vessels of the choroid extend into the retina. This rapid neovascularization of the retina leads to leaky blood vessels that exude blood into the retina leading to more rapid photoreceptor death. The wet stage, in particular, results in total vision loss, thus, deemed more severe than the dry form. There is strong evidence to suggest that all reported cases of wet AMD occur due to the progression of the disease from the dry AMD stage. Thus, the most efficient way of preventing the severe wet form of AMD is to treat the condition while in the dry stage, hindering the progressing of the disease past the less severe stage.
To date, extensive research on the treatment of AMD using laser technology has been performed. Previous attempts to treat AMD using laser therapy include photodynamic therapy and photocoagulation treatment [2]. In photodynamic therapy, a photosensitizer is administered and then excited with a laser source. Due to the excitation of the photosensitizer material, it stimulates the production of free radicals that induce cell death of the desired tissue. In the treatment of AMD, the photosensitizer is injected into the leaky blood vessels where it is absorbed by the endothelial cells of the blood vessels. Once the photosensitizer is excited, cell death is induced in the endothelial cells, slowing the progression of the exudative blood vessels within the retina. In photocoagulation the laser is used to cauterize the leaky blood vessels in the retina. These previous methods of treatment are both hindered by the same shortcomings: lack of specificity and targeting only the final stage of the condition, when a significant amount of vision loss has already occurred. Both forms of treatment target the exudative vessels in the retina but are characterized by large-scale collateral damage within the retina. While the laser in photodynamic therapy can be targeted at certain areas of the retina, the photosensitizer is not tissue selective in which cells uptake the sensitizer. Thus, any cell containing the photosensitizer that the laser beam hits will be exposed to free radicals and go through apoptosis; leading to excessive cellular death around the desired target. Photocoagulation leaves large-scale lesions on the retina, and a potential side effect of these lesions is the loss of peripheral vision. Therefore, an attempted treatment for the loss of central vision can potentially lead to the loss of the patient's peripheral vision. To date, there has not been a successful treatment developed to prevent the progression of AMD by targeting the early dry stages of the condition.
In recent years, researchers have made some advances in the treatment of AMD. More specifically, Dr. Guymer et al. at the Macular Research Unit, Centre for Eye Research at the University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia discovered that by exposing the macula to nanosecond (billionth of a second long) laser pulses, significant macular regeneration was observed. According to this Australian group, the laser treatment eliminated drusen in the treated eye and in so doing, reverses the degenerative process of AMD and save patients' sight. Fourteen patients have been followed to the 6-month mark. Of these, 10 patients had improved visual function or drusen removal. The researchers attribute the regeneration mechanism to the improvement of the transport properties of the Bruch's membrane hydraulic conductivity where the laser radiation triggers retinal pigmented epithelial cells to change. The Australian group asserts that the key to such a treatment is the use of nanosecond-long laser pulses to cause retinal pigmented epithelium cells to be destroyed without damaging adjacent health cells.
The Australian group claim to be blasting cells within the RPE layer using a nanosecond laser. This blasting of the retina induces the formation of micro-bubbles within the RPE cells causing cell death without rupturing the cell membrane, in order to stimulate rejuvenation of the RPE layer. The Australian group report not only improvement of the retinal function in AMD patients, but also regression of the disease [3]. Within the claims of their retinal rejuvenation mechanism they state that damaging the cells within the RPE induces a reparative cellular response, which results in improvement of the transport capabilities of the Bruch's membrane. Within the claims of a patent application for retinal rejuvenation it is stated that the group is killing RPE cells, inducing the migration of RPE cells into the targeted region and stimulating an improvement in the transport capabilities of the Bruch's membrane [3]. In a different publication it is stated that the laser pulses stimulate a natural cellular reparative process in the RPE cells, leading to the RPE functional rejuvenation without inducing cell death [4]. Thus, it is not clear whether the reparative process kills the cells or not. However, both of these suggested tissue repair processes are unlikely, as it is an established fact that the RPE cells of the central retina have no inherent biological rejuvenation systems and they do not reproduce [5-8]. This leads to the conclusion that the rejuvenation mechanism is still poorly understood, thus, it is still not clear if this treatment mechanism results in the regression of the disease.
Furthermore, the claim that nanosecond-long laser pulses can deliver a significant amount of energy without heat delivery, and thus thermal damage, is likely incorrect. Nanosecond laser pulse will damage healthy cells and the neuro-retina layer as the energy is deposited over a long time (longer than the electron energy relaxation time).
Therefore, what is needed is an improved system and method for laser-based treatment that addresses some of the limitations in the prior art and renders laser-AMD treatment to be more effective.